Download Is it General Paresis?

Controversies in Geriatric Medicine
Is it General Paresis?
_____________________________________________________
Abdulrazak Abyad
Correspondence:
A. Abyad, MD, MPH, MBA, AGSF , AFCHSE
CEO, Abyad Medical Center
President, Middle-East Academy for Medicine of AgingCoordinator, Middle-East Primary Care Research
Network
Coordinator, Middle-East Network on Aging
Email: [email protected]
“Knowing syphilis in all its manifestations and relations, and
all other things clinical will be added into you”.
ABSTRACT
Sir William Osler, 1897
The manifestations of central nervous system syphilis
are unfamiliar to a differential of patients with dementia to many physicians today as a result of the relative
rarity of this condition. This is a report of a patient
with syphilis and dementia in an 88 year old Hispanic
female. General Paresis is a progressive disease of brain
leading to mental and physical deterioration. The clinical manifestations usually appear about 15-20 years
after primary infection. It is important to keep tertiary
syphilis in the differential diagnosis of dementia.
Syphilis is one of the most interesting diseases of humans.
The disease has been of great historical significance for the
practice of medicine, and for many persons who played important roles in the history of western world (1). Syphilis has
expanded rapidly during the past two decades. The increase
started gradually in the 1970s, due to the alteration in sexual
behavior. The overall incidence increased slowly until 1982
and then declined slightly until 1986 (2). The number of reported cases of syphilis, including primary, secondary and
congenital syphilis, has been rapidly rising since 1987 (3,4).
Case Report
Key words: Syphilis, Paresis, Dementia
This is a report of a patient with syphilis and dementia. An
88 year old Hispanic female presented with multiple problems.
The daughter noted over the last year that her mother became
less talkative than before. She is quite most of the time and she
is usually not oriented to time, place and person. She still remembers the immediate family, but she cannot engage in long
conversations. Her Folstein Mini-Mental score was 17/30, her
geriatric depression scale was 14/30. Other associated problems include urinary incontinence and gait disturbance. Her
neurological examination revealed: The left pupil is 7 millimeters with minimal reaction to light. The right pupil was 45
millimeters and reactive to light. Normal heart sounds S1 and
S2, regular rhythm with no gallop or rail. Unequal pupils with
one of them reactive to light; the other not reactive, pupils react normally to convergence accommodation. The rest of the
cranial nerves were intact with good gag reflex. Reflexes are
+2 all over; no nystagmus. Babinski was positive on the left
side, muscle power was 3/5, unsteady gait. Laboratory study
revealed a positive VDRL, a positive FTA. Her CT scan of the
brain was normal. Ophthalmology examination revealed interstitial keratitis. The patient was hospitalised in 1987. Lumbar
puncture was attempted three times but failed. She received
treatment with IV penicillin for 10 days.
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The Stages of Syphilis
Primary Syphilis:
The typical lesions (Chancre) of the untreated illness
typically appears from 10 to 90 days (average 3
weeks) from exposure. The lesion is normally single
but may be multiple, and while it is normally painless
and connected with regional adenopathy, exceptions
occur (5).
Secondary Syphilis:
Classically, secondary Syphilis is featured by
macular or papular lesions on the palms and soles.
Nevertheless, the rash frequently begins on the trunk
and spreads to the extremities ultimately embracing
the whole body. It usually evolves six to eight weeks
after the chancre has healed (2). It is also linked
with systemic symptoms, including low grade fever,
malaise, myalgia and generalised lymphadenopathy
(6). Meningitis, iritis, glomulerulonephritis and
hepatitis are infrequent but potential manifestations
of secondary syphilis (Table 1) (5). The differential
diagnosis of secondary Syphilis is broad, which
accounts for the disease’s historical name as “the
great imitator” (5). The family of the patient did not
recall any illness that resembles the above.
Latent Syphilis:
The latent stage has no clinical manifestations. It
is divided into an early phase and a late phase. The
Centers for Disease Control currently uses a one year
cutoff to differentiate between early and late latent
infection (2). Latent Syphilis follows the secondary
stage of infection in the untreated patient. Roughly
25% of patients in the early latent stage will have
at least one relapse of mucocutaneous symptoms,
which may be helpful in the clinician’s evaluation
and management (7). Up to 35 percent of untreated
persons with latent syphilis acquire the late sequelae
of tertiary syphilis (7).
Tertiary Syphilis
Tertiary Syphilis is an ongoing, inflammatory
disease that can effect any organ system. Among the
untreated patients in the Oslo study who progressed
to tertiary disease, cardiovascular Syphilis developed
in 10%, neurosyphilis in 10% and gummatous
Syphilis in 15% (7).
Neurosyphilis
The manifestation of the central nervous system
readily recognised by practicing physicians three or
four decades ago are unfamiliar to many physicians
today as the result of relative rarity of this condition,
as happened with our patient. A helpful schema for
classification of neurosyphilis is shown in (Table 2).
Although this classification indicates the existence
of distinctive individual forms of neurosyphilis,
features of several of the entities commonly coexist.
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Long-term longitudinal studies performed earlier in this century
revealed that out of 953 persons with primary or secondary
syphilis, 6.5 percent subsequently developed CNS involvement
(8,9). The most common forms of nervous system involvement
were asymptomatic neurosyphilis (31%) and tabes 30%. The
incidence of paresis was most likely underrated since such
patients were more probable to have been treated in psychiatric
rather than general hospitals.
General Paresis
General paresis is a meningoencephalitics associated with true
invasion of the cerebrum by T. Pallidum. The clinical illness
is a chronic process that may present in middle or late adult
life. The course is progressively downhill, in untreated patients.
This form of late Syphilis develops 15 to 20 years after initial
infection. Patients with this disease made up to 5 to 10 percent of
all first admissions of psychotic patients to psychiatric hospitals
prior to World War II. (9,10).
Symptoms and Signs
The clinical picture is an aggregation of neurologic findings
and psychiatric symptoms. It can imitate nearly any type of
psychiatric or neurological disorder. It is usually insidious in
onset. The early characteristics are normally of psychiatric kind,
and the trend of illness is that of a dementing process. Initial
manifestations embody progressive memory loss, worsening
of intellectual function and personality changes which was
the case in our patient. Other symptoms include defects in
judgement, emotional lability, delusions, and inappropriate
social or moral behavior, in our case there were no delusional
symptoms. Depression in some studies has been reported as the
predominant presenting feature and the most common initial
diagnosis in patients with paresis (11). The patient was clinically
depressed, with a GDS of 14/30.
In patients with paresis of apparently sudden clinical onset,
the earliest indication of the disease may be seizures,
transient ischemic attacks, or an apparent stroke with loss of
consciousness (apoplectiform attack), followed by hemiparesis,
monoplegia, or aphasia. Pupillary abnormalities are among the
most common neurologic findings in general paresis (Table 3
- next page). Speech gets continuously thicker, and the issue
may be complicated by the development of global aphasia. A
true Argyll Robertson pupil is not common in early paresis; at
this stage the pupil may be large (rather than miotic), unequal,
and sluggishly reactive to light and accomodation. Gradually,
normal pupils can turn to Argyll Robertson type that was
present in this patient, characterised by:
(1) The retina is sensitive (i.e., eye is not blind);
(2) Pupils are small, fixed and do not react to strong light;
(3) Pupils react normally to convergence-accommodation;
(4) Mydriatics (atropine) fail to dilate pupil fully;
(5) Pupils do not dilate on painful stimuli.
Apathy, hypotonia, unsteadiness, dementia, and physical
deterioration become the major elements in the clinical picture,
as the disease advances. Recurrent focal or generalized seizures
accompany progressive deterioration resulting in bedridden,
paralyzed, incontinent state. The term Lisauer’s dementia
paralytica describes a small group of atypical cases of paresis
which showed focal neurological signs and on autopsy exposed
impressive atrophy of certain cerebral convolution (9), especially
in the frontal and temporal lobes. Such patients formerly had
focal seizures followed by hemiparesis, hemianopia, or aphasia
which thereafter cleared.
The duration of untreated paresis, from the onset of detectable
mental symptoms till death, has ranged from a few months, in
cases of sudden onset, to 4 or 5 years (9). Spontaneous remissions
in mental symptomatology have happened infrequently, but
have not changed the ultimate course of the disease. In the prepenicillin era, treatment of paresis with malaria plus arsenicals
benefited 33 to 50 percent of cases by arresting progression of
the disease and allowing some type of occupational activity.
The shorter the duration, and the milder the symptoms at the
institution of therapy, the better the prognosis. In this lady
treatment started late and no amelioration of symptoms was
noted after treatment.
A few cases of general paresis, despite treatment with large
doses of penicillin, have communicating hydrocephalus as a
complication. This leads to either lack of clinical amelioration
or gradual worsening. These patients develop gait apraxia,
akinetic mutism, incontinence and pyramidal tract signs
along with severe dementia (12). CSF shunting causes prompt
amelioration in several cases. Diminished CSF absorption by
chronic meningitis and meningeal fibrosis in general paresis
seems to be the cause for this process.
Laboratory Findings
The blood nontreponemal serology has been reported positive
in 95 to 100 percent of cases of paresis (9,12). In another study,
only 48.5 percent of patients with a diagnosis of neurosyphilis
had a positive nontreponemal serology (13). However, 56.3
percent of patients had a history of earlier treatment of syphilis.
Thus, this series may not be as conflicting with other studies
as it seems, since earlier treatment may have been adequate
to cause seroconversion (without preventing the subsequent
development of neurosyphilis). The serum FTA-ABS test is
uniformly positive in patients with paresis. In our case both
VDRL and FTA were positive.
CSF abnormalities are present in practically all cases of
untreated paresis (9). The characteristic CSF findings, include
the following:
(1) Normal or, occasionally, slightly increased pressure;
(2) Lymphocytic pleocytosis (usually 8 to 100 lymphocytes per
cubic millimeter);
(3) Increased protein concentration usually 50 to 100 mg/dl)
(4) Increased globulin concentration;
(5) Positive colloidal gold reaction, when performed
(6) Normal or occasionally, mildly reduced glucose; and
(7) Reactive nontreponemal test.
The CSF nontreponemal tests show a very high specificity, and
false positive VDRL test is remarkably exceptional. Thus, a
positive CSF VDRL test is a powerful indication for a diagnosis
of neurosyphilis. However, CSF nontreponemal tests may have
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a sensitivity of less than 100 percent. In some patients with
clinically diagnosed neurosyphilis (14), CSF Wassermann reactions have been reported negative. This can happen in a patient
whose neurosyphilis process has been confined by treatment
leaving steady mental changes.
In a few clinically characteristic cases of neurosyphilis (15)
CSF VDRL may be negative, and the entire CSF analysis may
be normal. Although abnormalities occur in the CSF of 25 to
40 percent of patients with untreated secondary syphilis (16),
designating early association of nervous system, treatment with
penicillin usually prevents any progression to symptomatic
neurosyphilis. CSF FTA-ABS may be reactive as a product of
diffusion of serum syphilis, therefore there are problems with
the specificity of this test (17). False positive reactions occur
in 0.5 to 4.5 percent. In addition, a reactive CSF FTA-ABS result may not indicate active neurosyphilis, since the reactivity
may be produced by diffusion of serum immunoglobulins into
the CSF (18). Also contamination of a CSF specimen with very
small amounts of FTA-positive blood can produce a false positive CSF FTA test (19). For these reasons the interpretation of a
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positive CSF FTA test is unclear (20). At present, a positive CSF
FTA test alone in a patient with neurologic findings of uncertain
nature does not establish a diagnosis of neurosyphilis.
In patients with paresis EEG is abnormal in 80 percent of cases.
Recently CT scan has been utilized to assess cerebral syphilis (21). Findings on CT scan range from extensive regions of
decreased attenuation of the cerebral white matter, particularly
in the frontal lobes and paraventricular areas of parietal lobes
to enlargement of cortical sulci and associated ventricular dilation (21). These findings resemble the CT scan pattern observed
in demyelinating disorders. Other CT findings include cortical
atrophy and multiple areas of hypodensity in both cerebellar
hemispheres and in the brain stem (these findings are consistent with infarctions) (21). Godt et al (22) found both enhancing
lesions (gummas) and generalized cortical and subcortical atrophy in several patients with neurosyphilis. Chest roentgenograms may show widening of the aorta, consistent with syphilitic aortitis, which occasionally coexists with parenchymatous
neurosyphilis.
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Diagnosis and Differential Diagnosis
The clinical picture, is easily distinguishable in its full-blown
form, however is more hard to ascertain when atypical or incomplete. Spinal fluid alterations usually help in the diagnosis.
The CSF is abnormal in all untreated cases of general paresis,
but the same alterations can happen in the middle of other neurosyphilis. Hence, the association of preexisting CSF alterations
of asymptomatic syphilitic meningitis with a diversity of organic brain syndromes can be misdiagnosed as general paresis. These include cerebral tumor, subdural hematoma, cerebral
arteriosclerosis, Alzheimer’s disease, multiple sclerosis, senile
dementia, and chronic alcoholism. CT scan findings, the presence of pupillary changes, and a history of drug or alcohol abuse
are useful in accurate diagnosis. Hallucinations are important
in delirium tremens but are unusual in general paresis. However alcoholic worsening and Korsakoff’s psychosis can present
a picture of memory loss, unsuitable conduct, mood swings, and
faulty opinion that is hard to differentiate from paresis.
An adult-onset seizure disorder can be a presentation of paresis
or of an exceptional form of neurosyphilis. Paresis may be ruled
out when CSF irregularities are lacking. When CSF alterations
of neurosyphilis are present, the inquest change to whether the
seizures symbolize epilepsy in a patient with asymptomatic
neurosyphilis or whether they are the presentations of syphilitic
brain injury. The presence of focal neurologic findings in patients with neurosyphilis-produced seizures aids in answering
the question.
Management
ANTIBIOTIC THERAPY
The management of neurosyphilis and outcome has markedly
improved since the introduction of penicillin. In a multicenter
study including treatment of over 1000 patients with paresis,
a total penicillin dosage of six million units was judged to be
satisfactory (23). Patients who required re-treatment to arrest
the infection had received less than six million units of penicillin initially. In the past decade it has been recognized that
the treatment with 7.2 million units of benzathine penicillin G
(2.4 million units intramuscularly weekly for 3 doses) is sufficient treatment for all kinds of neurosyphilis. The most recent recommendations of the Centers of Disease Control (24)
involve the use of either intraveneous aqueous penicillin G for
10 days, intramuscular procaine penicillin G for 10 days, or
weekly injections of benzathine penicillin G for 3 doses (Table
4) (24). Intravenous penicillin G for 10 to 15 days is the most
reasonable therapy to employ for symptomatic or asymptomatic
neurosyphilis. This assures penicillin concentrations in CSF
which are continuously at least several fold above the minimally
treponimicidal concentration of 0.018 microgram per milliliter
during therapy (25, 26). Alternatively, daily aqueous procaine
penicillin G (plus probenecid) for 10 to 14 days would be preferable to benzathine penicillin G, that is no longer recommended
by the World Health Organization.
FOLLOW-UP AND RE-TREATMENT
The CSF data are normally a reliable index of the activity of
neurosyphilis and furnish a gauge of the efficacy of the antibiotic therapy. When initial penicillin therapy has stopped the infection, repeat CSF examination at 3 to 6 months reveals normal
cell count and, if initially elevated, a decline in concentration of
protein (27).
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One year after treatment CSF examination reveals a persistent
fall in the protein level and a decrease in the titer of the nontreponemal serologic test. However, the latter may not become
completely negative for several years or longer and is not an indication of active neurosyphilis under these circumstances. In
three to six months if the CSF cell count does not return to normal or if, having returned to normal, the count rises again in relapse, then re-treatment is indicated. If relapse has not occurred
during a period of 2 years after adequate penicillin therapy, it is
unlikely to occur. Subsequently, reexamination should be done
annually for several years. Blood serologic testing should be
performed at 6 and 12 months and afterwards at yearly intervals
for at least 3 years (28).
PROGNOSIS
The natural history of the disease is progressive, and the result is ultimately deadly. The span of life from the beginning
of tangible mental symptoms to death normally extends from
a few months to 4 or 5 years, but an infrequent treated patient
with so-called stationary paresis has survived for 10 years (9).
Recent studies involving longer term follow-up indicate the development of new neurosyphilis signs in 39 percent of patients
treated with penicillin (29). Advancement of the disease can
happen indeed in the absence of reactive CSF tests. It is equivocal whether the evolution of new signs in patients with paresis
treated with what has been determined adequate penicillin dosage is due to persistence of treponemes in the CSF, to the need
for spirochetocidal concentrations of penicillin in the CSF (30,
31), or to an increased susceptibility to other neurologic processes. More study of these treatment failures is required.
Conclusion
Syphilis is still prevalent, especially in particular sectors of the
population. Late complications can be somewhat less of an issue than the preantibiotic era, however vigilance to the probability of late Syphilis and appreciation of clinical manifestations of late Syphilis are crucial if these forms of disease are
to be diagnosed and treated adequately. The main consideration must be vigilance in finding, treating, and preventing early
Syphilis. Since all forms of Syphilis, especially certain types of
late Syphilis, are less common than the glory days of Syphilis
as a clinical specialty, it is important to educate others and to
remind ourselves of the multiple faces of the great actor, lues
venerea.
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